• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6339-6342
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• 2014

Background: The incidence of rectal cancer is increasing in younger age groups. Limited data is available regarding survival outcome in younger patients with conflicting results from western world. The goal of this study was to determine survival in patients with rectal cancer <30 years of age and compare it with their older counterparts in the Pakistani population. Materials and Methods: A retrospective chart review of patients operated for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided into two groups, Group 1 aged ${\leq}30years$ and Group 2 aged >30years. Patient characteristics, surgical procedure, histopathological details and number of loco-regional and distant failures were compared. Expected 5 year survival was calculated using Kaplan Meier curves and significance was determined using the Log rank test. Results: There were 38 patients in group 1 and 144 in group 2. A significantly high number of younger patients presented with poorly differentiated histology (44.7% vs 9.7%) (p=0.0001) and advanced pathological stage (63.1% vs 38.1%) (p=0.04). Predicted overall 5 year survival was 38% versus 57% in groups I and II, respectively (p=0.05). Disease free survival was 37% versus 52% and was significantly different (p=0.007). Conclusions: Early onset rectal cancer is associated with poor pathological features and a worse outcome in Pakistani population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1599-1603
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• 2012

Objectives: Since methylenetetrahydrofolate reductase (MTHFR) maintains the balance of circulating folate and methionine and blocks the formation of homocysteine, its regulation in relation to different cancers has extensively been studied in different populations. However, information on Pakistani breast cancer patients is lacking. The MTHFR gene has two most common mutations that are single nucleotide additions which result in change of amino acids C677T to Ala222val and A1298C to Glu429Ala. Methodology: 110 sporadic breast patients with no prior family history of cancer or any other type of genetic disorders along with 110 normal individuals were screened for mutations in exons 1 to exon 9 using single strand conformational polymorphism, RFLP and sequencing analyzer. Results: The p values for the 677CC, 677CT, and 677TT genotypes were 0.223, 0.006, and 0.077, respectively. Those for the 1298AA, 1298AC, and 1298CC genotypes were 0.555, 0.009, and 0.003, respectively. Conclusions: We found an overall a significant, weak inverse association between breast cancer risk and the 677TT genotype and an inverse association with the 1298C variant. These results for MTHFR polymorphism might be population specific in sporadic breast cancer affected patients but many other factors need to be excluded before making final conclusions including folate intake, population and disease heterogeneity.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3907-3909
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• 2014

Background: Cytogenetic abnormalities have important implications in diagnosis and prognosis of acute leukemia and are now considered an important part of the diagnostic workup at presentation. Karyotype, if known at the time of diagnosis, guides physicians to plan appropriate management strategies for their patients. Aim and Objectives: To determine the cytogenetic profile of acute lymphoblastic leukemia (ALL) in Pakistani children in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (<15years old) diagnosed at Aga Khan University from January 2006 to June 2011 was performed. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 153 patients were diagnosed as ALL during the study period, of which 127 samples successfully yielded metaphase chromosomes. The male to female ratio was 1.8:1. A normal karyotype was present in 51.2% (n=65) of the cases whereas 48.8% (n=62) had an abnormal karyotype. Most of the abnormal cases showed hyperdiploidy(13.4%) followed by t(9;22)(q34;q11.2) (7.08%). Conclusions: This study revealed a relative lack of good prognostic cytogenetic aberrations in Pakistani children with ALL.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1535-1537
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• 2016

Background: Primary myelodysplastic syndrome (MDS) is an acquired clonal disorder of myeloid progenitor cells, characterized by peripheral cytopenias in the presence of hypercellular marrow with dysplastic features. Our aim was to study the demographical and clinicopathological features of adult Pakistani patients with MDS at disease presentation. Materials and Methods: This single centre study was conducted at Liaquat National Hospital and Medical College, extending from January 2010 to December 2014. Data were retrieved from the patient archives. Results: Overall 45 patients were diagnosed at our institution with de novo MDS during the study period. There were 28 males and 17 females. Age ranged between 18 and 95 years with a mean age of $57.6{\pm}17.4years$ and median of 64 years. The male to female ratio was 1.7:1. The main presenting complaints were generalized fatigue (60%), fever (33.3%), dyspnea (15.5%), bleeding (13.3%) and weight loss (11.1%). Examination was unremarkable in 42.2% of patients. Physical examination revealed pallor in 37.7%, followed by petechial and purpuric rashes in 20%. The commonest laboratory finding was anemia (hemoglobin < 10 g/dl in 41 (91.1%) patients. Out of these, 27 (60%) patients had normocytic anemia, followed by macrocytic (22.2%) and microcytic (8.8%). Conclusions: Primary MDS in Pakistani patients demonstrates a male preponderance. The proportion of anemic patients was high in our series with predominance of normocytic anemia. However, other clinico-hematological features appear comparable to published data.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2299-2304
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• 2012

Since there is evidence that human papillomavirus (HPV) may play some role in oral carcinogenesis, we investigated the presence of HPV in a group of Pakistani subjects with normal oral cavity using real-time PCR analysis. Two-hundred patients attending the Dental Department, Sandaman Provincial Hospital, Balochistan, Pakistan, were recruited. After interview, oral epithelial cells were collected by scraping and subjected to DNA extraction. The HPV-positive DNA samples were further analyzed using primer sets specific for HPV-16 and -18. It was found that out of 200 DNA samples, 192 were PCR-positive for the ${\beta}$-globin gene and these were subsequently examined for the presence of HPV DNA. Among these, 47 (24.5%) were HPV-positive with the virus copy number ranged between 0.43-32 copies per 1 ${\mu}g$ of total DNA (9-99 copies per PCR reaction). There were 4 and 11 samples containing HPV-16 and -18, respectively. Additionally, one sample harbored both types of HPV. Among the investigated clinical parameters, smoking habit was associated with the presence of HPV (p = 0.001) while others indicated no significant association. The prevalence of HPV in normal oral cavity in our Pakistani subjects appears to be comparable to other studies. However, the association between the presence of HPV and smoking warrants further investigations whether both of these factors can cooperate in inducing oral cancer in this group of patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.277-280
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• 2014

Background: Testicular cancer management is considered a marvel of modern science with excellent treatment results. Pakistan has a distinct ethnic variation and geographic distribution but data regarding clinical presentation of testicular tumors and their management is under reported. The objective of this study was to determine clinical profile, treatment modalities and survival outcome of testicular tumors in the Pakistani population. Materials and Methods: A retrospective review of patients who received treatment for testicular cancer at Shaukat Khanum Cancer Hospital from January 2009 to December 2012 was performed. Patient demographics, clinical features at presentation and treatment modalities were assessed. For categorical variables chi square test was used. Survival was calculated using Kaplan Meier survival curves and Log rank test was employed to determine significance. Results: The most common tumor was mixed germ cell tumor in 49% patients. For all tumor variants except seminoma, stage III was the most common clinical stage at presentation. Majority of patients with non seminomatous germ cell tumors presented in the15-30 year age group as compared to seminoma which was most prevalent in the 30-40 year age group. Orchiectomy followed by chemotherapy was the most common treatment modality in 80% patients. Expected 5 year survival for seminomas and non-seminomatous germ cell tumors was 96% and 90% respectively which was not significantly different (p=0.2). Conclusions: Despite a distinct clinical profile of testicular tumors in Pakistani population, survival is comparable with published reports.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.4
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• pp.1581-1585
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• 2015

Human papillomaviruses (HPVs) remain a serious world health problem due to their association with cervical and head and neck cancers. While over 100 HPV types have been identified, only a few subtypes are associated with malignancies. HPV 16 and 18 are the most prevalent oncogenic types in head and neck cancers. Although it has been proven that some subsets of benign and malignant head and neck lesions are associated with HPV, the general population have very little awareness and knowledge of their association with HPV. Therefore, the purpose of this study was to determine the knowledge of HPV and its links with head and neck benign and malignant lesions in a group of Pakistani dental patients who attended the Dental Department of the Sandeman provincial hospital in Quetta, Pakistan. One hundred and ninety-two patients were recruited and requested to answer a questionnaire. It was revealed that there was a low level of knowledge about HPV and its association with head and neck benign and malignant lesions among the participants. This result suggested that more education regarding the relationship of HPV in inducing head and neck benign and malignant lesions is required in this group of patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9495-9498
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• 2014

Background: The difference in prognosis of adult and childhood acute lymphoblastic leukemia (ALL) can be attributed largely to variation in cytogenetic abnormalities with age groups. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of the patients. Aim and Objectives: To determine the frequency of cytogenetic abnormalities in Pakistani adult patients with ALL in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (${\geq}15$years old) diagnosed at Aga Khan University from January 2006 to June 2014 was performed. Phenotype (B/T lineage) was confirmed in all cases by flow cytometry. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 166 patients were diagnosed as ALL during the study period, of which 151 samples successfully yielded metaphase chromosomes. The male to female ratio was 3.4:1. The majority (n=120, 72.3%) had a B-cell phenotype. A normal karyotype was present in 51% (n=77) of the cases whereas 49% (n=74) had an abnormal karyotype. Of the abnormal cases, 10% showed Philadelphia chromosome; t(9;22)(q34;q11.2). Other poor prognostic cytogenetic subgroups were t(4;11)(q21;q23), hypodiploidy (35-45 chromosomes) and complex karyotype. Hyperdiploidy (47-57 chromosomes) occurred in 6.6%; all of whom were younger than 30 years. Conclusions: This study showed a relatively low prevalence of Philadelphia chromosome in Pakistani adults with ALL with an increase in frequency with age (p=0.003). The cumulative prevalence of Philadelphianegative poor cytogenetic aberrations in different age groups was not significant (p=0.6).

• BMB Reports
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• v.37 no.5
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• pp.552-555
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• 2004

Several studies have demonstrated the importance of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms in the pathogenesis of hypertension. This study sought to determine the association between the ACE I/D polymorphism and essential hypertension in young Pakistanis. The frequency of the ACE I/D polymorphism was established by a comparative cross-sectional survey of Pakistani patients suffering from essential hypertension and ethnically matched normotensive controls. Samples were collected from tertiary care hospitals in northern Pakistan. Hypertensive individuals were defined as those with a systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg on three separate occasions, or those currently receiving one, or more, anti-hypertensive agents. DNA samples obtained from hypertensive (n=211) and normotensive (n=108) individuals were typed by PCR. The frequency of the ACE I/I genotype was significantly higher in hypertensive patients, aged 20-40 years, than in normotensive controls of the same age group ($\chi^2$ = 4.0, P = 0.041). Whereas no overall significant differences were observed between the I/I, I/D and D/D ACE genotypes (One way ANOVA, F=0.672; P=0.413). The association between the ACE I/I genotype and essential hypertension in individuals aged $\leq$ 40 years suggests that ACE has a role in early onset essential hypertension in Pakistan.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8629-8631
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• 2016

Background: Primary idiopathic myelofibrosis (PMF) is a clonal Philadelphia chromosome-negative myeloproliferative neoplasm characterized by extramedullary hematopoiesis and marrow fibrosis. It is an uncommon hematopoietic malignancy which primarily affects elderly individuals. The rational of this study was to determine its clinico-epidemiological profile along with risk stratification in Pakistani patients. Materials and Methods: In this retrospective cross sectional study, 20 patients with idiopathic myelofibrosis were enrolled from January 2011 to December 2014. Data were analyzed with SPSS version 22. Results: The mean age was $57.9{\pm}16.5years$ with 70% of patients aged above 50. The male to female ratio was 3:1. Overall only 10% of patients were asymptomatic and the remainder presented with constitutional symptoms. In symptomatic patients, major complaints were weakness (80%), weight loss (75%), abdominal discomfort (60%), night sweats (13%), pruritus (5%) and cardiovascular accidents (5%). Physical examination revealed splenomegaly as a predominant finding detected in 17 patients (85%) with the mean splenic span of $22.2{\pm}2.04cm$. The mean hemoglobin was $9.16{\pm}2.52g/dl$ with the mean MCV of $88.2{\pm}19.7fl$. The total leukocyte count of $17.6{\pm}19.2{\times}10^9/l$ and platelets count were $346.5{\pm}321.9{\times}10^9/l$. Serum lactate dehydrogenase, serum creatinine and uric acid were $731.0{\pm}154.1$, $0.82{\pm}0.22$ and $4.76{\pm}1.33$ respectively. According to risk stratification, 35% were in high risk, 40% in intermediate risk and 25% in low risk groups. Conclusions: The majority of PMF patients were male and presented with constitutional symptoms in our setting. Risk stratification revealed predominance of advanced disease in our series.